Safety Study of Clinical and Immune Effects of Phosphodiesterase 4 (PDE-4) Inhibitor in Cutaneous Lupus Patients

Discoid cutaneous lupus is the most common cutaneous manifestation of lupus erythematosus, a
chronic, immune mediated disease of unknown etiology. The immune processes underlying
cutaneous lupus remain largely unexplored, but recent evidence suggests a role for dendritic
cells (DCs), type 1 interferons (IFN) and Th1-type immune processes. Treatment of cutaneous
lupus remains limited primarily to anti-malarials, with thalidomide an effective secondary
agent. However, side effects associated with these treatments are potentially problematic
with chronic use. Phosphodiesterases (PDE) are critical enzymes that degrade cAMP. In
particular, PDE type 4 (PDE4) activity is found in inflammatory and immune cells, including
DCs. The immune modulator CC-10004 is a PDE4 inhibitor with demonstrated low toxicity in
phase I and II clinical studies with potential efficacy in cutaneous lupus. CC-10004 is a
well-tolerated, selective PDE4 inhibitor with demonstrated inhibitory effects on Th1-type
cytokines and other inflammatory mediators and is under development for the treatment of
inflammatory and immune mediated conditions. Prior studies include pilot trials in psoriasis
and exercise-induced asthma, with results suggesting clinical efficacy in the former study.
This open label, pilot study of 16 weeks duration will explore the clinical and
immune-modulating effects of CC-10004 in 10 cutaneous discoid lupus patients. Patients
meeting study criteria will receive the drug for 12 weeks, followed by a 4-week washout
period. Study visit time points will include weeks 0, 1, 2, 4, 6, 8, 10, 12 and 16, during
which we will measure outcomes for clinical, immunological and safety parameters. To
investigate early immunological changes occurring in response to treatment, we will also
perform skin punch biopsies of lesional sites at week 0 and week 4 for immunohistochemical
and molecular analysis.

Inclusion Criteria:

- Diagnosis of cutaneous discoid lupus by clinical and histopathological exam

Exclusion Criteria:

- Systemic lupus involving the internal organs

- Systemic vasculitis

- History of other clinically significant disease process

- History of HIV, hepatitis B or C

- Concurrent use of immune modulating therapy

- Evidence of incompletely treated tuberculosis

- Pregnant or lactating female